Objective—To develop a simple extractionless method for detection of rosiglitazone in canine plasma and test the method in a pharmacokinetic study after oral administration of rosiglitazone in dogs.
Animals—3 client-owned dogs with cancer.
Procedures—High-performance liquid chromatography-tandem mass spectrometry was performed on canine plasma. The 3 dogs with cancer in the pharmacokinetic study were assessed via physical examination and clinicopathologic evaluation and considered otherwise healthy. Food was withheld for 12 hours, and dogs were administered a single dose (4 mg/m2) of rosiglitazone. Plasma was collected at various times, processed, and analyzed for rosiglitazone.
Results—The developed method was robust and detected a minimum of 0.3 ng of rosiglitazone/mL. Mean ± SD maximum plasma concentration was 205.2 ± 79.1 ng/mL, which occurred at 3 ± 1 hours, and mean ± SD elimination half-life was 1.4 ± 0.4 hours. The area under the plasma rosiglitazone concentration-versus-time curve varied widely among the 3 dogs (mean ± SD, 652.2 ± 351.3 ng/h/mL).
Conclusions and Clinical Relevance—A simple extractionless method for detection of rosiglitazone in canine plasma was developed and was validated with excellent sensitivity, accuracy, precision, and recovery. The method enabled unambiguous evaluation and quantitation of rosiglitazone in canine plasma. This method will be useful for pharmacokinetic, bioavailability, or drug-drug interaction studies. Oral rosiglitazone administration was well tolerated in the dogs.
To establish the pharmacokinetics of a single 2-mg oral dose of chlorambucil in cats with indolent lymphoproliferative malignancies.
24 client-owned cats.
Cats were assigned to 1 of 4 groups, with each group having a total of 3 sample collection time points over 12 hours after receiving a single 2-mg oral dose of chlorambucil. Each time point combined to generate 6 full patient plasma chlorambucil concentration-time curves from the 24 cats. Chlorambucil treatment was continued every other day and a single, variably timed sample collection was obtained on day 14. Population parameter estimates were obtained by nonlinear mixed-effects modeling. Covariates investigated included age, sex, baseline serum cobalamin, study location, weight, and body condition score.
Chlorambucil administered orally to cats was found to have a peak plasma concentration of approximately 170 ng/mL (SE, 31.1 ng/mL), percent coefficient of variation (%CV) of 18.4% within 15 minutes, and a terminal half-life of 1.8 hours (SE, 0.21 hour; %CV, 12.4). At the 4-hour mark, a smaller secondary peak in plasma chlorambucil was found. Day 14 samples were similar to those of the initial dose. No covariates showed a significant effect in the population model.
In these cats, chlorambucil at a 2-mg dose administered every other day undergoes rapid gastrointestinal absorption and plasma clearance with no drug accumulation between doses. These data are critical to inform future work investigating the association of chlorambucil drug exposure with adverse events and outcome of cats with lymphoproliferative diseases.
Objective—To determine prevalence, reason for evaluation, treatment, and outcome for dogs and cats with presumed solitary ocular lymphoma (PSOL).
Design—Retrospective case series.
Animals—7 dogs and 2 cats with PSOL.
Procedures—Medical records were reviewed. Progression-free survival time (PFST) and overall survival time (OST) were determined.
Results—Animals with intraocular (4 dogs and 1 cat) or conjunctival (3 dogs and 1 cat) lymphoma represented 0.1% and 0.08% of patients with lymphoma evaluated at the hospital during the study period, respectively. Animals with intraocular lymphoma represented 0.19% of all patients with uveitis; animals with conjunctival lymphoma represented 0.16% of all patients with conjunctivitis. Tumors included B-cell (2 intraocular and 1 conjunctival), non–B-cell, non–T-cell (1 intraocular), and T-cell (3 conjunctival) neoplasms; immunophenotype of 2 uveal lymphomas was not determined. Treatments included enucleation (4 intraocular) and chemotherapy (3 intraocular and 2 conjunctival). All dogs with intraocular lymphoma developed neurologic signs. Lymph node metastasis was detected in 2 patients with conjunctival lymphoma. Median PFST and OST were 178 days for all animals with PSOL, dogs with PSOL, and animals with intraocular lymphoma. Median PFST and OST for animals with conjunctival lymphoma were 221 and 549 days, respectively.
Conclusions and Clinical Relevance—Results indicated PSOL was uncommon, but should be considered a differential diagnosis for animals with uveitis or conjunctivitis. Performance of MRI and cytologic analysis of CSF and regional lymph node aspirate samples may be beneficial for such patients. Prognosis seemed to be better for animals with conjunctival lymphoma than it was for those with intraocular lymphoma.
Objective—To reexamine (via immunohistochemical techniques) canine tissue samples that had been previously classified as gastrointestinal leiomyosarcomas (GILMSs), identify and differentiate gastrointestinal stromal tumors (GISTs) from GILMSs, and compare the biological behavior and clinical course of GISTs and GILMSs in dogs.
Design—Retrospective case series.
Procedures—Medical records of 42 dogs for which a histologic diagnosis of GILMS was confirmed were reviewed for signalment, clinical signs, physical examination findings, results of initial diagnostic tests, surgical findings, adjunctive treatment, location of the tumor, completeness of resection, and outcome after surgery. Archived tumor tissue specimens from each dog were restained via immunohistochemical techniques to differentiate tumor types. Long-term follow-up information was obtained from the medical record or through telephone interviews with owners and referring veterinarians.
Results—On the basis of immunohistochemical findings, 28 of 42 tumors were reclassified as GISTs and 4 were reclassified as undifferentiated sarcomas; 10 tumors were GILMSs. In dogs, GISTs developed more frequently in the cecum and large intestine and GILMSs developed more frequently in the stomach and small intestine. Median survival times for dogs with GISTs and GILMSs were 11.6 and 7.8 months, respectively; if only dogs surviving the perioperative period were considered, median survival times were 37.4 and 7.8 months, respectively. These differences, however, were not significant.
Conclusions and Clinical Relevance—In dogs, many previously diagnosed GILMSs should be reclassified as GISTs on the basis of results of immunohistochemical staining. The biological behavior of these tumors appears to be different.
OBJECTIVE To determine survival time and metastatic rate for dogs with early-stage anal sac adenocarcinoma (ASACA) treated with surgery alone and assess whether specific clinical, pathological, or immunohistochemical factors were predictive of outcome for those dogs.
DESIGN Retrospective case series.
ANIMALS 34 dogs with early-stage, nonmetastatic ASACA that were treated with surgery only.
PROCEDURES Medical record databases of 2 referral hospitals were searched to identify dogs examined between 2002 and 2013 that had a diagnosis of nonmetastatic ASACA that was < 3.2 cm at its largest diameter. Only dogs that received surgical treatment alone were included in the study. For each dog, information extracted from the medical record included signalment, clinical and diagnostic test findings, tumor characteristics, and outcome. When available, archived tumor specimens were histologically reviewed and tumor characteristics were described; Ki-67 and E-cadherin expressions were evaluated by use of immunohistochemical methods. Clinical, pathological, and immunohistochemical factors were assessed for associations with survival time and tumor recurrence and metastasis rates.
RESULTS Median survival time was 1,237 days. Seven dogs had tumor recurrence and 9 dogs developed metastatic disease at a median of 354 and 589 days, respectively, after primary tumor removal. Cellular pleomorphism was positively associated with development of metastatic disease. No other factors evaluated were associated with outcome.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated dogs with early-stage nonmetastatic ASACA generally had a favorable outcome following surgical removal of the primary tumor alone. Routine rectal examination may be a simple and useful method for detection of dogs with early-stage ASACA.
Objective—To evaluate changes in characteristics of feline injection-site sarcomas (ISSs) from 1990 through 2006.
Design—Retrospective case series.
Animals—392 cats with a histologic diagnosis of soft tissue sarcoma, osteosarcoma, or chondrosarcoma at potential injection sites.
Procedures—Classification and anatomic location of tumors and signalment of affected cats were compared between ISSs diagnosed before and after publication of the Vaccine Associated Feline Sarcoma Task Force vaccination recommendations in 1996.
Results—From before to after publication of the vaccination recommendations, proportions of ISSs significantly decreased in the interscapular (53.4% to 39.5%) and right and left thoracic (10.2% to 3.6% and 9.1% to 1.3%, respectively) regions. On the other hand, proportions of ISSs significantly increased in the right thoracic limb (1.1% to 9.5%) and the combined regions of the right pelvic limb with right lateral aspect of the abdomen (12.5% to 25.0%) and the left pelvic limb with left lateral aspect of the abdomen (11.4% to 13.8%). Patterns of tumor classification and signalment did not change.
Conclusions and Clinical Relevance—Despite publication of the vaccination recommendations, a high proportion of tumors still developed in the interscapular region. There was also an increase in lateral abdominal ISSs, which are more difficult to treat and are likely attributable to aberrant placement of injections intended for the pelvic limbs. Veterinarians are complying with vaccination recommendations to some extent, but they need to focus on administering vaccines as distally as possible on a limb to allow for complete surgical margins if amputation of a limb is required.
To describe the procedure of prostatic artery embolization (PAE) in dogs with prostatic carcinoma and to evaluate the short-term outcome for treated dogs.
20 client-owned dogs with prostatic carcinomas between May 2014 and July 2017.
In this prospective cohort study, dogs with carcinoma of the prostate underwent PAE with fluoroscopic guidance. Before and after PAE, dogs underwent CT and ultrasonographic examinations of the prostate, and each owner completed a questionnaire about the dog's clinical signs. Results for before versus after PAE were compared.
Prostatic artery embolization was successfully performed in all 20 dogs. Tenesmus, stranguria, and lethargy were significantly less common 30 days after PAE (n = 2, 1, and 0 dogs, respectively), compared with before PAE (9, 10, and 6 dogs, respectively). Median prostatic volume was significantly less 30 days after PAE (14.8 cm3; range, 0.4 to 48.1 cm3; interquartile [25th to 75th percentile] range, 6.7 to 19.5 cm3), compared with before PAE (21.7 cm3; range, 2.9 to 77.7 cm3; interquartile range, 11.0 to 35.1 cm3). All dogs had a reduction in prostatic volume after PAE, with a median prostatic volume loss of 39.4% (95% CI, 20.3% to 59.3%).
CONCLUSIONS AND CLINICAL RELEVANCE
Prostatic artery embolization was associated with decreased prostate volume and improved clinical signs in this cohort. The short-term response to PAE appears promising, and evaluation of the long-term impact on survival time is needed.
OBJECTIVE To evaluate potential associations between surgical approach and complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma.
DESIGN Retrospective case series.
ANIMALS 107 client-owned cats.
PROCEDURES Medical records of cats that underwent surgical excision of mammary adenocarcinoma by means of a unilateral or bilateral (staged or single-session) mastectomy at 9 hospitals between 1991 and 2014 were reviewed. Relevant clinicopathologic data and details of surgical and adjuvant treatments were recorded. Outcome data were obtained, including postoperative complications, progression-free survival time, and disease-specific survival time.
RESULTS Complications occurred in 12 of 61 (19.7%) cats treated with unilateral mastectomy, 5 of 14 (35.7%) cats treated with staged bilateral mastectomy, and 13 of 32 (40.6%) cats treated with single-session bilateral mastectomy. Complications were significantly more likely to occur in cats undergoing bilateral versus unilateral mastectomy. Median progression-free survival time was longer for cats treated with bilateral mastectomy (542 days) than for cats treated with unilateral mastectomy (289 days). Significant risk factors for disease progression included unilateral mastectomy, tumor ulceration, lymph node metastasis, and tumors arising in the fourth mammary gland. Significant risk factors for disease-specific death included lymph node metastasis and development of regional or distant metastasis. Among cats that did not develop metastasis, unilateral mastectomy was a significant risk factor for disease-specific death. Treatment with chemotherapy was associated with a significantly decreased risk of disease-specific death.
CONCLUSIONS AND CLINICAL RELEVANCE Results supported bilateral mastectomy for the treatment of mammary adenocarcinoma in cats to improve progression-free and disease-specific survival time. Performing bilateral mastectomy in a staged fashion may help to decrease the complication rate.